Gene & Cell Therapy for Cancers: The Promise of Chimeric Antigen Receptor (CAR)-T Cells

Prof. Taruna Ikrar

Authors

Prof. Taruna Ikrar Defenses University Republic of Indonesia, Bogor, Indonesia Author

Keywords:

Pharmacology, Gene & Cell Therapy, Chimeric Antigen Receptor T-Cells (CAR-T), Dendritic Vaccines, Cancers

Abstract

The pharmacology of cell and genetic therapy represents a highly advanced and contemporary treatment technology, capable of addressing the root causes of numerous diseases with remarkable accuracy and precision at the DNA and molecular levels. Genetic technology aims to develop treatments for genetic disorders caused by inherited genetic mutations, which affect millions of people worldwide and are often life-threatening terminal illnesses. Moreover, pharmacologists and genetic biologists are striving to treat hereditary disorders. By integrating cell and genetic molecular biology, scientists have developed Chimeric Antigen Receptor T-Cell (CAR-T) technology, which has been approved for the treatment of blood cancer. Cell-based and genetic therapy is a groundbreaking therapeutic approach poised to become a cornerstone in the future treatment of degenerative and malignant diseases, particularly cancer, congenital or genetic disorders.

Downloads

Download data is not yet available.

Author Biography

Prof. Taruna Ikrar, Defenses University Republic of Indonesia, Bogor, Indonesia

Faculty of Medicine

Faculty of Medicine, Malahayati University, Lampung, Indonesia

Aivita Biomedical, Irvine, California, USA

References

1. El-Deiry WS, Goldberg RM, Lenz H-J, et al. The current state of molecular testing in the treatment of patients with solid tumors, 2019. CA Cancer J Clin 2019; 69:305-43.

2. Richard L. Schilsky, M.D., and Dan L. Longo, M.D. Closing the Gap in Cancer Genomic Testing. NEJM 2022; 2109-2110.

3. Ylä-Herttuala, S., and Baker, A.H. (2017). Cardiovascular Gene Therapy: Past, Present, and Future. Mol. Ther. 25, 1095-1106.

4. Wist S, Berger SI, Iyengar R. Systems pharmacology and genome medicine: a future perspective. Genome Medicine 2009, 1:11: 1-9.

5. Papanikolaou E, Bosio A. The Promise and the Hope of Gene Therapy. Frontier in Gene therapy 2021: 1-11.

6. Milone MC, Bhoj VG. The Pharmacology of T Cell Therapies. Molecular Therapy: Methods & Clinical Development 2018; 08: 210-221.

7. Allan KM, et al. Treatment of Cystic Fibrosis: From Gene- to Cell-Based Therapies. Frontier in Pharmacology 2021: 12: 1-12.

8. Alejandrina Hernández-López et. al. Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope. Front. Pharmacol. 2021: 1-19.

9. Ikrar T. Functional impact of altered charge and/or size of amino acid residue at the selectivity filter of KCNQ1 potassium channel: Insight into gene therapy for severe QT phenotype. Dissertation Thesis 2008; Niigata University Library; 1-99.

10. Ikrar T, Guo N, He K, Besnard A, Levinson S, Hill A, Lee HK, Hen R, Xu X, Sahay A. Adult neurogenesis modifies excitability of the dentate gyrus. Front Neural Circuits. 2013: 26; 7:204: 1-15.

11. Sun Y, Ikrar T, Davis MF, Gong N, Zheng X, Luo ZD, Lai C, Mei L, Holmes TC, Gandhi SP, Xu X. Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity. Neuron. 2016 Oct 5;92(1):160-173

12. Garcia-Junco-Clemente P, Ikrar T, Tring E, Xu X, Ringach DL, Trachtenberg JT. An inhibitory pull-push circuit in frontal cortex. Nat Neurosci. 2017 Mar;20(3):389-392.

13. Kuhlman SJ, Olivas ND, Tring E, Ikrar T, Xu X, Trachtenberg JT. A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex. Nature. 2013 Sep 26;501(7468):543-6.

14. Nistor GI, Dillman RO, Robles RM, Langford JL, Poole AJ, Sofro MAU, Nency YM, Jonny J, Yana ML, Karyana M, Lestari ES, Triwardhani R, Mujahidah M, Sari RK, Soetojo NA, Wibisono D, Tjen D, Ikrar T, Sarkissian G, Winarta H, Putranto TA, Keirstead HS. A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses. Hum Vaccin Immunother. 2022 Nov 30;18(6):2100189.

15. Aizawa Y, Mitsuma W, Ikrar T, Komura S, Hanawa H, Miyajima S, Miyoshi F, Kobayashi Y, Chinushi M, Kimura A, Hiraoka M, Aizawa Y. Human cardiac ryanodine receptor mutations in ion channel disorders in Japan. Int J Cardiol. 2007 Mar 20;116(2):263-5.

16. Ikrar T, Shi Y, Velasquez T, Goulding M, Xu X. Cell-type specific regulation of cortical excitability through the allatostatin receptor system. Front Neural Circuits. 2012 Jan 20; 6:2-11.

17. Ikrar T, Hanawa H, Watanabe H, Okada S, Aizawa Y, Ramadan MM, Komura S, Yamashita F, Chinushi M, Aizawa Y. A double-point mutation in the selectivity filter site of the KCNQ1 potassium channel results in a severe phenotype, LQT1, of long QT syndrome. J Cardiovasc Electrophysiol. 2008 May;19(5):541-9.

18. Putranto TA, Wibisono D, Astoro NN, Ikrar T. Introducing the tolerogenic macrophage therapy as an alternative approach to manage systemic lupus erythematosus: a case series. Bali Medical Journal (Bali Med J) 2019, Volume 8, Number 3: 610-616.

19. Lazaro MT, Taxidis J, Shuman T, Bachmutsky I, Ikrar T, et al. Reduced Prefrontal Synaptic Connectivity and Disturbed Oscillatory Population Dynamics in the CNTNAP2 Model of Autism. Cell Rep. 2019 May 28;27(9):2567-2578.

20. Anurogo D, Parikesit AA, Ikrar T. LncRNAs in CONDBITs Perspectives, From Genetics towards Theranostics (LncRNAs Dalam Perspektif CONDBITs, Dari Genetik ke Theranostik). Jurnal Sains Kesihatan Malaysia 17(2) 2019: 1-16.

21. Putranto TA, Ikrar T, Waskito P. Regenerative Macrophages: A New Hope For Cardiomyopathy. Periodico Tche Quimica 2019: 17:35: 1207-1217.

22. Liau LM et al. Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination with Extension of Survival Among Patients with Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial. JAMA Oncol. 2022 Nov 17: e225370.

23. Muftuoglu Y, Liau LM. Results From the Checkmate 143 Clinical Trial: Stalemate or New Game Strategy for Glioblastoma Immunotherapy? JAMA Oncol. 2020 Jul 1;6(7):987-989.

24. Ikrar T, Anurogo D. The Art of Oncoimmunovaccinomics. World Journal of Vaccines, 2021, 11, 50-66.

25. Brown CE, Bucktrout S, Butterfeld, et al. The future of cancer immunotherapy for brain tumors: a collaborative workshop. Journal of Translational Medicine (2022) 20:236.

26. Datsi A, Sorg RV. Dendritic Cell Vaccination of Glioblastoma: Road to Success or Dead End.

Front Immunol. 2021 Nov 2; 12:770390.

27. Bota D et al. Tumor Markers Associated with Increased Survival in a Phase II Trial of Dendritic Cell/ Tumor-Initiating-Cell Vaccine AV-GBM-1 in Patients with Newly Diagnosed Glioblastoma. J Immunother Cancer 2021;9(Suppl 2): A1–A1054

28. Galluzzi, L., et al. (2014) Classification of Current Anticancer Immunotherapies. Oncotarget, 5, 12472.

29. Hernández-López A. Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope. Front. Pharmacol. 2021: 12: 1-18.

30. Ikrar, T. Functional impact of altered charge and/or size of amino acid residue at the selectivity filter of KCNQ1 potassium channel: Insight into gene therapy for severe QT phenotype. Niigata University Library. 2008: 270 (I271/W4), 1-30.